CONICET | Buscador de Institutos y Recursos Humanos

Solid tumors are not simply clones of cancer cells. Instead, they are composed of multiple cells types and extracellular matrix. Interactions between tumor cells and the stroma influences disease initiation and progression. In thyroid cancer, there is little or no information on epithelial-stromal interaction. In preliminary studies, we found that thyroid tumor cell-fibroblasts (Fb) interaction promotes the secretion and activation of metalloproteinases (MMPs) and tumor cell migration. The aim of our work was to analyze the modulation of proteins related with MMPs expression and activation: TIMP-2, MT1-MMP and CD147 in thyroid cell-Fb co-culture. As an in vitro tumor-stroma cell interaction model, non-tumor cells (N-ThyOri), thyroid papillary carcinoma cells (TPC-1) and thyroid anaplastic cells (8505c) were co-cultured with normal Fb. TIMP-2 and MT1-MMP mRNA were studied by qRT-PCR. The expression and glycosylation of CD147 were assessed by immunoprecipitation, western blot and flow cytometry. We observed changes in the proportion of the expression levels of TIMP-2 related to MT1-MMP in Fb-N-ThyOri co-cultures, but no diferences in TIMP2 and MT1-MMP expression were detected in Fb- 8505c co-cultures. The analysis of Fb CD147 expression did not show any significant differences after its co-culture with TPC-1, 8505c and N-ThyOri cells. In addition, no changes in CD147 glycosylation profile was detected. Fb-thyroid tumor cell interaction modulates differentially the expression of proteins such as TIMP-2 and MT1-MMP which would be consistent with the observed changes in the profile of secreted and activated MMPs. These observations suggest the involvement of tumor cell - stroma interactions in thyroid carcinogenesis.